The biochemical modification of human neutrophil (PMN) microtubules/tubulin was studied by monitoring the specific stimulation of the post-translational incorporation of tyrosine into tubulin Alpha-chains, by the chemoattractant fmet-leu-phe and also by the Ca2+ ionophore A23187. The data indicate that both fmet-leu-phe and A23187 stimulate PMN tyrosinolation, which is abolished under anaerobic conditions and in the presence of various anti-oxidants and reducing agents. Studies in PMN from patients with the Chediak-Higashi syndrome and with chronic granulomatous disease indicated a greatly exaggerated response in the former and inhibited response in the latter. Based on studies of the oxidative state of the patients' cells and studies using oxidizing and reducing agents, it is concluded that there is a close association between PMN redox state and tubulin tyrosinolation. Results of recent studies also indicate the requirement of extracellular free Ca2+ and the cellular Ca2+ regulatory protein calmodulin, in the modulation of tubulin tyrosinolation in PMN. The data provide new insights into the relationship of PMN redox state and free Ca2+ concentration in modulation of tubulin tyrosinolation and neutrophil function.